Therapeutic Effect of Targeting Branched-Chain Amino Acid Catabolic Flux in Pressure-Overload Induced Heart Failure.

Background Branched-chain amino acid (BCAA) catabolic defect is an emerging metabolic hallmark in failing hearts in human and animal models. The therapeutic impact of targeting BCAA catabolic flux under pathological conditions remains understudied. Methods and Results BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid), a small-molecule inhibitor of branched-chain ketoacid dehydrogenase kinase, was used to enhance BCAA catabolism. After 2 weeks of transaortic constriction, mice with significant cardiac dysfunctions were treated with vehicle or BT2. Serial echocardiograms showed continuing pathological deterioration in left ventricle of the vehicle-treated mice, whereas the BT2-treated mice showed significantly preserved cardiac function and structure. Moreover, BT2 treatment improved systolic contractility and diastolic mechanics. These therapeutic benefits appeared to be independent of impacts on left ventricle hypertrophy but associated with increased gene expression involved in fatty acid utilization. The BT2 administration showed no signs of apparent toxicity. Conclusions Our data provide the first proof-of-concept evidence for the therapeutic efficacy of restoring BCAA catabolic flux in hearts with preexisting dysfunctions. The BCAA catabolic pathway represents a novel and potentially efficacious target for treatment of heart failure

2D-3D Interlaced Transformer for Point Cloud Segmentation with Scene-Level Supervision

We present a Multimodal Interlaced Transformer (MIT) that jointly considers 2D and 3D data for weakly supervised point cloud segmentation. Research studies have shown that 2D and 3D features are complementary for point cloud segmentation. However, existing methods require extra 2D annotations to achieve 2D-3D information fusion. Considering the high annotation cost of point clouds, effective 2D and 3D feature fusion based on weakly supervised learning is in great demand. To this end, we propose a transformer model with two encoders and one decoder for weakly supervised point cloud segmentation using only scene-level class tags. Specifically, the two encoders compute the self-attended features for 3D point clouds and 2D multi-view images, respectively. The decoder implements interlaced 2D-3D cross-attention and carries out implicit 2D and 3D feature fusion. We alternately switch the roles of queries and key-value pairs in the decoder layers. It turns out that the 2D and 3D features are iteratively enriched by each other. Experiments show that it performs favorably against existing weakly supervised point cloud segmentation methods by a large margin on the S3DIS and ScanNet benchmarks. The project page will be available at https://jimmy15923.github.io/mit_web/.Comment: ICCV 2023 (main + supp). Website: https://jimmy15923.github.io/mit_web

High-Frequency Ultrasound Imaging to Evaluate Liver Fibrosis Progression in Rats and Yi Guan Jian Herbal Therapeutic Effects

The animals used in liver fibrosis studies must usually be sacrificed. Ultrasound has been demonstrated to have the ability to diagnose hepatic fibrosis and cirrhosis in experimental small-animal models. However, few studies have used high-frequency ultrasound (HFU, 40 MHz) to monitor changes in the rat liver and other hollow organs longitudinally. In this study, liver fibrosis was induced by administering dimethylnitrosamine (DMN) in SD rats, aged 8 weeks, for three consecutive days per week for up to 4 weeks. A Chinese herbal medicine Yi Guan Jian (YGJ) was orally administered (1.8 g/kg daily) to DMN-induced liver fibrosis rats for 2 weeks. Compared with the normal control rats, rats treated with DMN for either 2 weeks or 4 weeks had significantly lower body weights, liver indexes and elevation of hydroxyproline, GOT, and GPT contents. YGJ herbal treatment remarkably prevented rats from DMN-induced liver fibrosis. The HFU scoring results among the normal controls, 2-week DMN-treated rats, 4-week DMN-treated rats, and combined 2-week YGJ therapy with 4-week DMN-treated rats also reached statistical significance. Thus, HFU is an accurate tool for the longitudinal analysis of liver fibrosis progression in small-animal models, and the YGJ may be useful in reversing the development of hepatic fibrosis